Abstract:

Objective To identify the phenotype and gene mutation in one Chinese pedigree with hereditary protein C deficiency, and explore the action mechanism of mutant site. Methods The plasma levels of protein C activity and protein C antigen of the propositus and family members were detected using chromogenic assay and ELISA respectively. All of the nine exons and intron-exon boundaries of PROC gene were amplified by PCR and analyzed by direct sequencing for the propositus. To the family members, only the exons with mutations were amplified and analyzed. The molecular mechanism of mutant site was explored through conformational analysis of protein before and after mutation. Results The plasma levels of protein C activity and protein C antigen of the propositus were 38% and 33.6% respectively. Gene sequencing revealed that there existed a heterozygous missense mutation [c.541T>G (p. Phe181Val)] and a nonsense mutation [c.595C>T (p.Arg199*)] on exon 7 of PROC gene of the propositus. The former caused the transformation from Phe to Val on site 181, and the latter led to the mutation from Arg to stop codon on site 199. The plasma levels of protein C activity of the father and son were 49% and 42.2% respectively, and those of protein C antigen were 90% and 97.4% respectively, and both had the same heterozygous nonsense mutation c.595C>T. The plasma level of protein C activity of the mother was 84.4%, that of protein C antigen was 100%, and there was missense mutation on site c.541T>G in exon 7. The levels of protein S: A and AT: A were in the normal range in all the members. Conclusion Inherited protein C deficiency is indicated by phenotype diagnosis and gene analysis for the propositus. Two mutations of the propositus are inherited from father and mother respectively, which may be the cause for protein C deficiency, and c.595C>T mutation may be the main cause of decrease in protein C activity.

Key words: venous thromboembolism, protein C, deficiency, gene